LAUSR

Study Objectives: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the pandemic, Coronavirus Disease 2019 (COVID-19), with many of those infected now facing the burden of prolonged symptoms after they have cleared the infection. The most debilitating of these, called post-acute sequelae of COVID-19 (PASC), known colloquially as long COVID, is thought to be linked to immune dysregulation due to harmful inflammation, with the exact causes being unknown. Given the oral-lung aspiration axis being a key factor to many respiratory infectious processes and the microbiome’s previous role in systemic inflammation, we aimed to examine the relationship between the oral microbiome and the duration of symptom, including development of long COIVD. Methods: Symptom duration was determined via follow-up among a cohort of emergency department patients admitted to the hospital for COVID-19 infection. Tongue swabs were collected from patients presenting with symptoms concerning for COVID-19 infection. Patients with confirmed COVID-19 infection were followed until resolution of all symptoms. Bacterial composition of oral samples was determined by metagenomic sequencing. We used random forest classification modeling to identify microbiota and clinical covariates that associate with longer duration of symptoms. Results: Of the 31 patients followed, 17 developed ongoing symptomatic COVID-19 (symptoms > 4 weeks) and 10 went on to long COVID (symptoms>8 weeks). Patients with prolonged symptoms had higher abundances of microbiota that induce inflammation, such as members of the genera Prevotella and Veillonella. Notable is the increased abundances of species that produce inflammation causing lipopolysaccharides and the similarity of long COVID patients’ oral microbiome to those of patients with chronic fatigue syndrome. Conclusion: This is the first study to describe the microbiome’s association with long COVID and explore the possibility that the oral microbiome may play a role in this disease.